Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines

被引:17
作者
Ortiz, Cristian M. [1 ]
Ito, Tetsuo [2 ]
Hashimoto, Yosuke [3 ]
Nagayama, Satoshi [4 ]
Iwai, Akira [4 ]
Tsunoda, Shigeru [4 ]
Sato, Fumiaki [5 ]
Martorell, Miguel [1 ]
Angel Garcia, Jose [1 ]
Perez, Ana [1 ]
Shimada, Yutaka [6 ]
机构
[1] Univ Valencia, Hosp Gen Univ Valencia, Dept Pathol, Valencia 46014, Spain
[2] Sugita Genpaku Mem Obama Municipal Hosp, Dept Surg, Fukui 9178567, Japan
[3] Shizuoka Canc Ctr Hosp, Div Colon & Rectal Surg, Nagaizumi, Shizuoka 4118777, Japan
[4] Kyoto Univ, Grad Sch Med, Dept Surg, Sakyo Ku, Kyoto 6068507, Japan
[5] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Nanobio Drug Discovery, Sakyo Ku, Kyoto 6068507, Japan
[6] Toyama Univ, Dept Surg & Sci, Grad Sch Med & Pharmaceut Sci Res, Toyama 9300194, Japan
关键词
ACTIN-BUNDLING PROTEIN; FOCAL ADHESION KINASE; IN-VIVO; EXPRESSION; CANCER; MOTILITY; FAK; OVEREXPRESSION; INVASIVENESS; HOMOLOG;
D O I
10.1186/1746-1596-5-41
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Background: Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation. Methods: We examined whether fascin is a potential target in ESCC using in vitro and in vivo studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line. Results: The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. In vivo, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation. Conclusions: These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.
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页数:10
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